Transdermal therapeutic systems (TTS) belong to the widely used methods of drug administration, which allow rate-controlled drug delivery and avoidance of first-pass metabolism in the liver Beside scopolamine, nitroglycerin (glyceryl trinitrate), nicotine, clonidine and fentanyl, also transdermal delivery of sex steroids for hormone replacement therapy and contraception is a well-known and popular method in daily clinical practice. It is estimated that approximately 20% of patients using transdermal estradiol may complain of adverse cutaneous side effects. Most of those reactions are mild or moderate, usually limited to the area of drug application. However, prolonged use may increase the chance of developing sensitization. The purpose of this review is to provide up-to date information on the spectrum of cutaneous reactions caused by TTS and the characteristics of potential contact allergens, including sex hormones. Proper management and prophylactic measures were also included.